全文获取类型
收费全文 | 166篇 |
免费 | 4篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 1篇 |
2015年 | 1篇 |
2014年 | 8篇 |
2013年 | 12篇 |
2012年 | 16篇 |
2011年 | 12篇 |
2010年 | 7篇 |
2009年 | 5篇 |
2008年 | 8篇 |
2007年 | 9篇 |
2006年 | 13篇 |
2005年 | 9篇 |
2004年 | 9篇 |
2003年 | 4篇 |
2002年 | 6篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
排序方式: 共有170条查询结果,搜索用时 15 毫秒
101.
Jennifer L. Meitzler Sara Hinde Botond Bánfi William M. Nauseef Paul R. Ortiz de Montellano 《The Journal of biological chemistry》2013,288(10):7147-7157
Intramolecular disulfide bond formation is promoted in oxidizing extracellular and endoplasmic reticulum compartments and often contributes to protein stability and function. DUOX1 and DUOX2 are distinguished from other members of the NOX protein family by the presence of a unique extracellular N-terminal region. These peroxidase-like domains lack the conserved cysteines that confer structural stability to mammalian peroxidases. Sequence-based structure predictions suggest that the thiol groups present are solvent-exposed on a single protein surface and are too distant to support intramolecular disulfide bond formation. To investigate the role of these thiol residues, we introduced four individual cysteine to glycine mutations in the peroxidase-like domains of both human DUOXs and purified the recombinant proteins. The mutations caused little change in the stabilities of the monomeric proteins, supporting the hypothesis that the thiol residues are solvent-exposed and not involved in disulfide bonds that are critical for structural integrity. However, the ability of the isolated hDUOX1 peroxidase-like domain to dimerize was altered, suggesting a role for these cysteines in protein-protein interactions that could facilitate homodimerization of the peroxidase-like domain or, in the full-length protein, heterodimeric interactions with a maturation protein. When full-length hDUOX1 was expressed in HEK293 cells, the mutations resulted in decreased H2O2 production that correlated with a decreased amount of the enzyme localized to the membrane surface rather than with a loss of activity or with a failure to synthesize the mutant proteins. These results support a role for the cysteine residues in intermolecular disulfide bond formation with the DUOX maturation factor DUOXA1. 相似文献
102.
The effects of intracerebroventricular administration of an 80 pmole dose of cholecystokinin octapeptide sulphate ester, unsulphated cholecystokinin octapeptide and their fragments were tested on the dopamine, norepinephrine and serotonin contents of the rat hypothalamus, mesencephalon, amygdala, septum, cerebral cortex and striatum, as well as on the plasma corticosterone level.Cholecystokinin octapeptide sulphate ester and the tyrosine-sulphate-methionine and tyrosine-sulphate-methionine-glycine fragments increased the dopamine and norepinephrine contents of the hypothalamus and mesencephalon. The same compounds increased the dopamine content of the amygdala, while they decreased the dopamine and norepinephrine concentrations in the striatum. The plasma corticosterone level was also increased. The unsulphated cholecystokinin octapeptide and its fragments had no effects on the brain monoamine contents and slight but not significant effect on the plasma corticosterone level.The data suggest that the presence of the tyrosine-sulphate-methionine dipeptide is essential in the effects of cholecystokinin octapeptide sulphate ester on the monoamine contents of different brain areas, as well as on the plasma corticosterone level. 相似文献
103.
Zoltán Timár Sándor Bottka Lajos Kovács Botond Penke 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):1131-1133
Abstract A new, hypoxanthine-conaining PNA monomer, PNAs and complementary DNAs were designed, produced and investigated by thermal denaturation studies in order to find the analogue of inosine at PNAs [1]. Thermodynamic data were determined with the van't Hoff method [2, 3]. The measured and computational values were correlated. 相似文献
104.
Aggregation of amyloid peptide (Abeta) has been identified as a major feature of the pathogenesis of Alzheimer's disease. Increased risk for disease is associated with increased formation of polymerized Abeta. Inhibition of formation of toxic (aggregated) form of Abeta is one of the therapeutic possibilities. Beta sheet breaker peptides (BSBs) fulfill the requirements of an effective inhibitor. After having attached to the Abeta molecules, BSBs can prevent aggregation of Abeta to polymeric forms (aggregates). In the present study, we performed molecular modelling of complex formation between Abeta and two BSB peptides. Our aim was to find proper binding sequences for the BSB peptides on Abeta and characterize them. A dimeric model of Abeta was also used to study the interaction of BSBs with the aggregated forms of Abeta and find the sequences responsible for the polymerization process. A fast and efficient computational method: molecular docking was used for the afore-mentioned purposes. 相似文献
105.
The rise of Next Generation Sequencing (NGS) technologies has transformed de novo genome sequencing into an accessible research tool, but obtaining high quality eukaryotic genome assemblies remains a challenge, mostly due to the abundance of repetitive elements. These also make it difficult to study nucleotide polymorphism in repetitive regions, including certain types of structural variations. One solution proposed for resolving such regions is Sequence Assembly aided by Mutagenesis (SAM), which relies on the fact that introducing enough random mutations breaks the repetitive structure, making assembly possible. Sequencing many different mutated copies permits the sequence of the repetitive region to be inferred by consensus methods. However, this approach relies on molecular cloning in order to isolate and amplify individual mutant copies, making it hard to scale-up the approach for use in conjunction with high-throughput sequencing technologies. To address this problem, we propose NG-SAM, a modified version of the SAM protocol that relies on PCR and dilution steps only, coupled to a NGS workflow. NG-SAM therefore has the potential to be scaled-up, e.g. using emerging microfluidics technologies. We built a realistic simulation pipeline to study the feasibility of NG-SAM, and our results suggest that under appropriate experimental conditions the approach might be successfully put into practice. Moreover, our simulations suggest that NG-SAM is capable of reconstructing robustly a wide range of potential target sequences of varying lengths and repetitive structures. 相似文献
106.
B Penke 《Acta physiologica Academiae Scientiarum Hungaricae》1976,47(4):279-283
The primary and secondary structure of the three kinds of gastrointestinal hormones, i.e. gastrin, cholecystokinin-pancreozymin and secretin are discussed. 相似文献
107.
108.
109.
Lorentzen D Durairaj L Pezzulo AA Nakano Y Launspach J Stoltz DA Zamba G McCray PB Zabner J Welsh MJ Nauseef WM Bánfi B 《Free radical biology & medicine》2011,50(9):1144-1150
A recently discovered enzyme system produces antibacterial hypothiocyanite (OSCN(-)) in the airway lumen by oxidizing the secreted precursor thiocyanate (SCN(-)). Airway epithelial cultures have been shown to secrete SCN(-) in a CFTR-dependent manner. Thus, reduced SCN(-) availability in the airway might contribute to the pathogenesis of cystic fibrosis (CF), a disease caused by mutations in the CFTR gene and characterized by an airway host defense defect. We tested this hypothesis by analyzing the SCN(-) concentration in the nasal airway surface liquid (ASL) of CF patients and non-CF subjects and in the tracheobronchial ASL of CFTR-ΔF508 homozygous pigs and control littermates. In the nasal ASL, the SCN(-) concentration was ~30-fold higher than in serum independent of the CFTR mutation status of the human subject. In the tracheobronchial ASL of CF pigs, the SCN(-) concentration was somewhat reduced. Among human subjects, SCN(-) concentrations in the ASL varied from person to person independent of CFTR expression, and CF patients with high SCN(-) levels had better lung function than those with low SCN(-) levels. Thus, although CFTR can contribute to SCN(-) transport, it is not indispensable for the high SCN(-) concentration in ASL. The correlation between lung function and SCN(-) concentration in CF patients may reflect a beneficial role for SCN(-). 相似文献
110.
Tjaart A. P. de Beer Roman A. Laskowski Sarah L. Parks Botond Sipos Nick Goldman Janet M. Thornton 《PLoS computational biology》2013,9(12)
The 1000 Genomes Project data provides a natural background dataset for amino acid germline mutations in humans. Since the direction of mutation is known, the amino acid exchange matrix generated from the observed nucleotide variants is asymmetric and the mutabilities of the different amino acids are very different. These differences predominantly reflect preferences for nucleotide mutations in the DNA (especially the high mutation rate of the CpG dinucleotide, which makes arginine mutability very much higher than other amino acids) rather than selection imposed by protein structure constraints, although there is evidence for the latter as well. The variants occur predominantly on the surface of proteins (82%), with a slight preference for sites which are more exposed and less well conserved than random. Mutations to functional residues occur about half as often as expected by chance. The disease-associated amino acid variant distributions in OMIM are radically different from those expected on the basis of the 1000 Genomes dataset. The disease-associated variants preferentially occur in more conserved sites, compared to 1000 Genomes mutations. Many of the amino acid exchange profiles appear to exhibit an anti-correlation, with common exchanges in one dataset being rare in the other. Disease-associated variants exhibit more extreme differences in amino acid size and hydrophobicity. More modelling of the mutational processes at the nucleotide level is needed, but these observations should contribute to an improved prediction of the effects of specific variants in humans. 相似文献